Pan-antagonists for the androgen receptor and androgen receptor mutants associated with anti-androgen withdrawal

Abstract

Disclosed herein are novel antagonists of the androgen receptor and androgen receptor mutations associated with clinical failure of currently prescribed anti-androgens and use of said antagonists in the treatment of conditions associated with inappropriate activation of the androgen receptor.

1. A compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein R 1  is hydrogen, fluorine, chlorine, bromine, cyano, hydroxy, methyl acrylate, or C 1 -C 6  alkyl optionally substituted with hydroxy;
 R 2  is hydrogen, hydroxy, fluoro, chloro, cyano, C 1 -C 5  alkanoate, C 1 -C 5  alkylamino, or 
 C 1 -C 6  alkyl optionally substituted with hydroxy or acrylate; and 
 R 3  is hydrogen, C 1 -C 6  alkyl, fluoro, chloro, bromo, or cyano. 
 
     
     
       2. The compound of  claim 1 , selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       3. A compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein R 4  is phenyl optionally substituted with hydroxy; C 1 -C 6  phenylalkyl; or benzyl optionally substituted with hydroxy, C 1 -C 6  alkoxy optionally substituted with methoxy or cyano, C 1 -C 6  alkyl, C 1 -C 5  alkanoate, or C 1 -C 5  alkylamine. 
     
     
       4. The compound of  claim 3 , selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       5. A pharmaceutical composition comprising a compound of  claim 1  or  3 . 
     
     
       6. A pharmaceutical composition comprising a compound of  claim 2  or  4 .